Early versus delayed antiretroviral therapy for HIV and tuberculosis co-infected patients: A systematic review and meta-analysis of randomized controlled trials

Objective: To compare important clinical outcomes between early and delayed initiation of antiretroviral therapy (ART) in adults who had a co-infection of human immunodeficiency virus (HIV) and tuberculosis (TB). Methods: We performed a systematic search for relevant publications on PubMed, EMBASE, and the International Clinical Trials Registry Platform. We included randomized controlled trials (RCTs) that compared early ART initiation (within four weeks after anti-TB treatment starting) and delayed ART initiation (after eight weeks but less than twelve weeks of anti-TB treatment starting) in the course of TB treatment. Pooled estimates with corresponding 95% confidence interval (95%CI) were calculated with random-effects model. Sensitivity analysis was performed to investigate the stability of pooled estimates. Results: A meta-analysis was evaluated from six RCTs with 2272 participants. Compared to delayed ART initiation, early ART initiation significantly reduces all-cause mortality in HIV-positive patients with TB [incidence rate ratio (IRR) 0.75, 95%CI 0.59 to 0.95; I² = 0.00%; p = 0.67], even though there is an increased risk for IRD [IRR 2.29, 95%CI 1.81 to 2.91; I²2 = 0.00%; p = 0.56]. Additionally, early ART initiation was not associated with an increased risk for grade 3-4 drug-related adverse events [IRR 0.99, 95%CI 0.83 to 1.18; I² = 0.00%; p = 0.56]. Conclusions: Although limited evidence, our results provide support for early ART initiation in the course of anti-TB treatment. However, more well-designed cohort or intervention studies are required to further confirm our findings.